BACKGROUND: It is discovered that trace elements in Chinese patent medicine play an important role in pharmaceutical efficacy and structural analysis. A new topic has been formed gradually in a further research on pharmaceutical efficacy and effective components of Chinese patent medicine in the view of inorganic trace elements. The fuzzy classified study on the interrelationship between trace and constant elements of Chinese herbs and therapeutic effects is to discuss the trace-element action of drugs in the holistic aspect of trace elenent and research rather scientifically the holistic coordination among trace elements in Chinese herbs.OBJECTIVE: To determine the contents of 21 kinds of trace and constant elements in Chinese patent medicines in the treatment of cardio-cerebral vascular disease. To study with fuzzy classified method the interdependence between trace, constant elements of drugs and therapeutic effects so as to provide a new approach for the quality evaluation of Chinese patent medicine.DESIGN: Testified observed study based on various Chinese patent medicines.SETTING: Chemistry teaching-research room in a university and department of cardiology in a general hospital of a chemical industrial group corporation.MATERIALS: Twenty-one kinds of common Chinese patent medicines for the treatment of cardio-cerebral vascular diseases in clinic, namely di' ao xinxuekang capsule(DXK), xueshuan xinmaining capsule(XMN), shan haidan capsule(SHD), buchang naoxintong capsule(NXT), linaoxin capsule(LNX), xinnaosu capsule(XNS), lixin wan(LXW), suxiao jiuxin wan (SJX), xinbao wan(XBW), yinxingye pian(YXY), fufang danshen pian (DSP), niuhuang jiangya wan(NHJY), naosaitong pian(NST), qiangli tianma duzhong wan ( TD W ) , tongsaimai pian ( TSM ) , tongmai ningxin infusion(TMNX), maitong capsule(MTC), fufang yinxing wan ( YXW ) , da huoluo dan(DHL), guanxin suhe capsule(GXSH) and xiaoshuan tongluo capsule (XSTL).METHODS: Wet digestion was used to manage samples, atomic absorption spectrophotometric method(AAS) method was used to determine the contents of 10 kinds of trace and constant elements in 21 Chinese patent medicines,namely Na, Ca, Mg, K, Fe, Cr, Ni, Cu, Zn and Mn. Data range method was applied for the standardized management of statistical indexes of various element contents in relevant drugs, dotprod(U, V) method was used to measure correlation coefficient(r) among the classified objects so as to determine fuzzy matrixes in universe. The interrelationship was analyzed between the contents of trace elements of various Chinese medicines and pharmaceutical efficacy. By the analysis of fuzzy matrixes in universe, it was to evaluate firmly on the efficacy similarity of various kinds of Chinese patent medicines with quantitative indexes.MAIN OUTCOME MEASURES: ① Results of element contents; ② Results of fuzzy cluster analysis on elements.RESULTS: The standardized management of statistical indexes was carried on the contents of Na, Ca, Mg, K, Fe, Cr, Ni, Cu, Zn and Mn in various drugs to determine correlation coefficient(r) among the classified objects so as to determine fuzzy matrixes in universe. When(r) = 0.55, there were 9 kinds of drugs similar in cluster, namely xueshuan xinmaining capsule, buchang naoxintong capsule, lixin wan, xin bao wan, qiangli tianmai duzhong wan,tongsaimai pian, maitong capsule, da h uoluo dan and xiaoshuan tongluo capsu le. When(r) =0. 65, there were 6 kinds of drugs similar in cluster,namely buchang naoxintong capsule, xin bao wan, qiangli tianmai duzhong wan, tongsaimai pian, maitong capsule and xiaoshuan tongluo capsule. When(r) =0. 87, there were 2 kinds of drugs similar in cluster, namely buchang naoxintong capsule and xin bao wan.CONCLUSION: It is indicated in the research that the drugs are in rich of trace and constant elements. The larger the correlation coefficient of drugs is,the more similar the pharmaceutical efficacy is. It is discovered the close interrelationship of the trace and constant elements in drugs with their pharmaceutical efficacy. In this research, fuzzy classified method is used to discuss, in the view of trace elements, the similarity of quantitative indexes in efficacy of Chinese patent medicine commonly administrated in the treatment of cardio-cerebral vascular disease, which has provided a new approach for the quality evaluation of Chinese patent medicine.

Objective To investigate the correlation between the baseline serum caveolin-1 (Cav-1) levels and the clinical outcome in patients with acute ischemic stroke at day 90 after onset. Methods Consecutive patients with acute ischemic stroke treated in hospital were enrolled. The Cav-1 levels were measured by the enzyme-linked immunosorbent assay. Functional outcomes were assessed at day 90 after onset using the modified Rankin Scale (mRS), and mRS 0-2 was defined as good outcome. The demographic and clinical characteristics of the good outcome group and the poor outcome group were compared. Multivariate logistic regression analysis was used to identify the correlation between the low serum Cav-1 levels and the poor outcome at day 90 after onset. Results A total of 169 patients with acute ischemic stroke were included in the analysis, including 116 males (68. 5% ). Their age ranged from 50 to 83 years (mean, 63. 4 ± 9. 1). The mean serum Cav-1 level was 5. 483 ± 2. 617 ng/ml. Eighty-three-patients (49. 1% ) were in the good outcome group and 86 (50. 9% ) were in the poor outcome group. Univariate analysis showed that the proportions of patients in subcortical infarct (60. 5% vs. 43. 4% ; χ2 = 4. 944, P = 0. 026) and diffusion-weighted imaging-Alberta Stroke Program Early CT Score, (DWI-ASPECT) ≤7 (58. 1% vs. 40. 9% ; χ2 = 4. 984, P = 0. 026), as well as age (65. 5 ± 8. 9 years vs. 61. 2 ± 10. 7 years; t = 2. 793, P =0. 006), baseline systolic blood pressure level (140. 6 ± 17. 2 mmHg vs. 134. 9 ± 13. 4 mmHg; t = 2. 368, P = 0. 019; 1 mmHg = 0. 133 kPa), and National Institutes of Health Stroke Scale (NIHSS) score (4. 8 ± 3. 4 vs. 3. 9 ± 2. 2; t = 2. 211, P = 0. 036) were significantly higher than those of the good outcome group, and the serum Cav-1 level was significantly lower than that of the good outcome group (4. 9 ± 2. 3 ng/ml vs. 6. 1 ± 2. 1 ng/ml; t = 2. 977, P = 0. 003). After adjusting for the related confounding factors, multivariate logistic regression analysis showed that the low Cav-1 level was an independent predictor of poor outcome at day 90 in patients with acute ischemic stroke (odd ratio, 1. 157, 95% confidence interval 1. 016-1. 319;P = 0. 028). Conclusion The low serum Cav-1 level is an independent predictor of poor outcome in patients with acute ischemic stroke.

Objective To investigate the correlation between subclinical hypothyroidism (SCH) and cerebral atherosclerosis burden in patients with large artery atherosclerotic stroke.Methods Consecutive inpatients with acute large artery atherosclerotic stroke were enrolled.SCH was defined as TSH 4.50-10.0 mU/L and serum thyroxine level was normal.Cerebral atherosclerosis burden score was used to evaluate the severity of cerebral atherosclerosis.The total score of 1 or 2 was defined as mild atherosclerosis,and >2 was defined as severe atherosclerosis.Univariate analysis and multivariate logistic regression analysis was used to evaluate the correlation between SCH and severe cerebral atherosclerosis.ResultsA total of 263 patients with large artery atherosclerotic stroke were enrolled,including SCH 62 (23.6%),mild atherosclerosis 119 (45.2%),and severe atherosclerosis 144 (54.8%).The age (63.6±10.9 years vs.60.5±11.4 years;t=2.274,P=0.024),homocysteine (17.10±6.20 μmol/L vs.15.63±5.17 μmol/L;t=2.058,P=0.041),National Institutes of Health Stroke Scale (NIHSS) score (8.0 [5.0-10.0]vs.6.0 [5.0-9.0];Z=2.059,P=0.039),as well as the proportions of patients with hypertension (72.9%vs.58.8%;χ2=5.812,P=0.016),smoking (38.2%vs.26.1%;χ2=4.366,P=0.037),and SCH (30.6%vs.15.1%;χ2=8.610,P=0.003) in the severe cerebral atherosclerosis group were significantly higher than those in the mild cerebral atherosclerosis group.Multivariate logistic regression analysis indicated that SCH was an independent risk factor for severe atherosclerosis in patients with large atherosclerotic stroke (odd ratio 3.345;95%confidence interval 1.692-6.612;P=0.001) after adjusting for age,sex,hypertension,smoking,homocysteine,and NIHSS score.ConclusionSCH is an independent risk factor for severe cerebral atherosclerosis in patients with large atherosclerotic stroke.

Objective:To investigate the correlation between the degree of hepatic fibrosis and early neurological deterioration (END) after intravenous thrombolysis in patients with acute ischemic stroke (AIS) and its predictive value.Methods:Patients with AIS received intravenous thrombolysis at Nanjing Jiangbei Hospital from January 2018 to March 2023 were retrospectively included. Hepatic fibrosis-4 index (FIB-4) was used to evaluate the degree of hepatic fibrosis in patients. FIB-4 ≥ 2.67 was defined as severe hepatic fibrosis. END was defined as an increase of ≥4 from baseline on the National Institutes of Health Stroke Scale (NIHSS) score within 24 h after intravenous thrombolysis. The relevant factors of END were analyzed through univariate analysis and multivariate logistic regression model. Receiver operating characteristic (ROC) curve was used to analyze the predictive value of FIB-4 for END. Results:A total of 313 patients were included, of which 184 (58.8%) were male, aged 64.8±11.8 years old. The median baseline NIHSS score was 6 (interquartile range, 4-9), and the median FIB-4 was 1.76 (interquartile range, 1.28-2.56). Forty-five patients (14.4%) experienced END. Multivariate logistic regression analysis showed that after adjusting for other confounding factors, higher FIB-4 was significantly independently correlated with END (odds ratio 2.121, 95% confidence interval 1.422-3.162; P=0.001). ROC curve analysis shows that FIB-4 has a good predictive value for END (the area under the curve 0.689, 95% confidence interval 0.595-0.784; P=0.001). The optimal cutoff value of FIB-4 was 1.82, and its sensitivity and specificity in predicting END were 71.1% and 54.9%, respectively. Conclusion:FIB-4 has good predictive value for END in patients with AIS after intravenous thrombolysis.

Objective:To investigate the correlation between malnutrition and early neurological deterioration (END) after intravenous thrombolysis in patients with acute ischemic stroke.Methods:Patients with ischemic stroke received intravenous thrombolysis in the Department of Neurology, Nanjing Jiangbei People's Hospital from January 2018 to December 2021 were retrospectively enrolled. Nutritional status was assessed by geriatric nutritional risk index (GNRI) and prognostic nutritional index (PNI). END was defined as an increase of ≥4 in the National Institutes of Health Stroke Scale score within 24 h after intravenous thrombolysis compared with the baseline value. The demographic and baseline clinical data of the patients in the END group and the non-END group were compared. Multivariate logistic regression analysis was used to determine the independent correlation between malnutrition and END. Results:A total of 256 patients were enrolled, including 156 males (60.9%), aged 65.6±12.0 years. According to GNRI and PNI, there were 122 (46.7%) and 62 (24.2%) patients with malnutrition respectively. END occurred in 37 patients (14.5%) during hospitalization. Multivariate logistic regression analysis showed that after adjusting for other confounding factors, there was a significant independent correlation between malnutrition and END after intravenous thrombolysis in patients with acute ischemic stroke (severe malnutrition as assessed by GNRI compared to normal nutritional status: odds ratio 5.736, 95% confidence interval 1.033-31.866, P=0.046; severe malnutrition as assessed by PNI compared to normal nutritional status: odds ratio 4.928, 95% confidence interval 1.589-15.282, P=0.006). Conclusion:Malnutrition is very common in patients with acute ischemic stroke and has a significant correlation with END after intravenous thrombolysis.

Objective:To investigate the relationship between plasma Dickkopf-1 and early neurological deterioration (END) and outcome in patients with acute ischemic stroke.Methods:From January 2020 to December 2020, consecutive patients with first-ever ischemic stroke form the Department of Neurology, Nanjing Jiangbei Hospital were included. All patients were hospitalized within 24 h after onset. END was defined as the National Institutes of Health Stroke Scale (NIHSS) score within 7 d after admission increased by ≥2 or motor function score increased by ≥1 compared with the baseline. Poor outcome was defined as the modified Rankin Scale score >2 at 90 d after onset. Multivariate logistic regression analysis was used to determine the independent correlation between plasma Dickkopf-1 and END and outcome. Receiver operating characteristic (ROC) curve was used to evaluate the predictive value of plasma Dickkopf-1 for END and poor outcome. Results:A total of 176 patients were enrolled, including 92 males (52.3%), aged 66.7±9.6 years. The median Dickkopf-1 was 4.30 μg/L, 52 patients (29.5%) developed END, and 81 (46.0%) had poor outcome. Multivariate logistic regression analysis showed that the higher Dickkopf-1 was an independent predictor of END (odds ratio [ OR] 1.696, 95% confidence interval [ CI] 1.223-2.351; P=0.002) and poor outcome ( OR 1.566, 95% CI 1.156-2.121; P=0.004). ROC curve analysis showed that plasma Dickkopf-1 had good predictive value for END, and its area under the curve was 0.717 (95% CI 0.634-0.801); the optimal cut-off value was 4.40 μg/L, and the corresponding predictive sensitivity and specificity were 71.2% and 60.5%, respectively. Dickkopf-1 also had good predictive value for poor outcome, and its area under the curve was 0.701 (95% CI 0.624-0.778); the optimal cut-off value was 4.25 μg/L, and the corresponding predictive sensitivity and specificity were 65.4% and 61.1%, respectively. Conclusion:Plasma Dickkopf-1 has good predictive value for END and poor outcome in patients with acute ischemic stroke.

Objective:To investigate the predictive value of thromboelastographic (TEG) parameters for early neurological deterioration (END) after intravenous thrombolysis in patients with acute ischemic stroke.Methods:Consecutive patients with acute ischemic stroke treated with intravenous thrombolysis in Nanjing Jiangbei People's Hospital between January 2017 and December 2019 were enrolled. They completed TEG examination within 24 h after admission. END was defined as an increase of 4 points or more from the baseline National Institutes of Health Stroke Scale (NIHSS) score within 24 h after admission. Univariate analysis was used to compare the demographic characteristics, baseline data, laboratory indicators and TEG parameters between the END group and the non-END group. Multivariate logistic regression analysis was used to determine the independent risk factors for END. Receiver operating characteristic (ROC) curve was used to evaluate the predictive value of different models for END. Results:A total of 174 patients with acute ischemic stroke were enrolled, aged (68.9±13.4) years, 111 (63.8%) were male, median baseline NIHSS score was 5.0, and 29 (16.7%) had END. Compared with the patients in the non-END group, the age, homocysteine, fasting blood glucose, high-sensitivity C-reactive protein (hs-CRP), baseline NIHSS score and the proportion of patients with diabetes mellitus and hemorrhagic transformation (HT) in the END group were significantly increased (all P<0.05), and the coagulation reaction time of TEG was significantly reduced ( P=0.005). Multivariate logistic regression analysis showed that after adjusting for confounding factors, age (odds ratio [ OR] 1.023, 95% confidence interval [ CI] 1.002-1.066; P=0.031), diabetes mellitus ( OR 2.627, 95% CI 1.021-7.176; P=0.041), higher hs-CRP level ( OR 1.050, 95% CI 1.018-1.083; P=0.002), HT ( OR 3.088, 95% CI 1.707-13.492; P=0.034) and TEG coagulation reaction time reduction ( OR 0.440, 95% CI 0.213-0.907; P=0.026) were the independent risk factors for END in patients with acute ischemic stroke receiving intravenous thrombolysis. ROC analysis showed that the area under the curve of the basic model composed of age, diabetes, hs-CRP level, and HT for predicting END was 0.766 (95% CI 0.665-0.871). When TEG coagulation reaction time was added to the basic model, the area under ROC curve for predicting END was increased to 0.816 (95% CI 0.733-0.899). Conclusion:The TEG coagulation reaction time reduction has a certain predictive value for END in patients with acute ischemic stroke receiving intravenous thrombolytic therapy.

Objective To investigate the correlations of P2Y12 gene polymorphisms with clopidogrel resistance and long-term outcome in patients with acute ischemic stroke. Methods From June 2015 to June 2017, consecutive patients with acute ischemic stroke admitted to the Department of Neurology, Nanjing Jiangbei People's Hospital were enrolled. Thromboelastography was used to measure platelet inhibition rate and assess clopidogrel resistance. Polymerase chain reaction was used to assay C34T and G52T polymorphisms of P2Y12 gene. The patients were followed up at 12 months after discharge. The primary outcome was combined outcome of stroke recurrence, myocardial infarction, and death due to cardiocerebrovascular events. Results A total of 214 patients were enrolled, 51 (23.8%) had clopidogrel re-sistance and 29 (13.4%) had major outcome events. One hundred twenty-eight (59.8%) patients were C34T CC genotype and 86 (40.2%) were CT+TT genotype. The proportion of clopidogrel resistance in patients with CT+TT genotype was significantly higher than that with CC genotype ( 76.5% vs.28.8%;χ2=25.672, P=0.001). There were 131 patients (61.2%) with G52T GG genotype and 83 (38.8%) with GT+TT genotype. There was no significant difference in the proportion of clopidogrel resistance between the GT+TT genotype and the GG genotype (43.1% vs.37.4%; χ2=0.534, P=0.465). Multiple logistic regression analysis indicated that age (odds ratio [OR] 1.064, 95%confidence interval [CI] 1.009-1.115;P=0.021), diabetes ( OR 3.773, 95%CI 1.672-8.475; P=0.004), and C34T CT+TT genotype ( OR 9.087, 95%CI 4.416-22.665; P=0.002) were the independent risk factors fot clopidogrel resistance. Cox proportional hazards model analysis showed that age (Hazard ratio [HR] 1.058, 95%CI 1.001-1.121; P=0.049), hypertension ( HR 3.105, 95%CI 1.149-9.523; P=0.028), homocysteine ( HR 1.101, 95%CI 1.020-1.190; P=0.014), and C34T CT+TT genotype ( HR 2.588, 95%CI 1.121-5.967; P=0.026) were independent risk factors for the composite outcome. Conclusion C34T polymorphism of P2Y12 gene in patients with acute ischemic stroke may be a risk factor for clopidogrel resistance and is independently associated with the risk of long-term recurrence of vascular events.